Locally Advanced or Metastatic Breast Cancer
Conditions
Brief summary
This study is a multicenter, open-label, phase 2 clinical study to evaluate the efficacy, safety and pharmacokinetics of YL202 in patients with locally advanced or metastatic breast cancer with TNBC, HR-positive, HER2-zero-expression or HER2-low-expression
Interventions
For each patient, YL202 should be intravenously infused over 60±10 min.
Sponsors
MediLink Therapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Have been informed of the study before the start of the study and voluntarily sign name and date on the informed consent form. 2. Patients with locally advanced or metastatic disease (according to the UICC and AJCC staging system \[Version 8\]) who are not candidates for curative surgery or radiotherapy. 3. Patients who are pathologically confirmed advanced/unresectable or metastatic breast cancer with HR-negative and HER2-negative,. 4. Patients who are confirmed HR positive and HER2-Zero-expression and HER2-Low-expression. 5. Breast cancer patients who have previously failed treatments of HER2-ADC or TROP2-ADC. 6. Have at least 1 extracranial measurable lesion as a target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 7. Have Adequate organ and bone marrow function within 7 days prior to the first dose. 8. Female patients of childbearing potential must agree to use highly effective contraception from screening throughout the duration of the study and for at least 6 months after the last dose of study drug. 9. Have a expected survival ≥ 3 months. 10. Have ability and willingness to comply with protocol-specified visits and procedures.
Exclusion criteria
1. Have prior treatment with an agent targeting HER3. 2. Have prior intolerance to treatment with topoisomerase I inhibitor or an ADC that consists of topoisomerase I inhibitor. 3. Have been enrolled in another clinical study concurrently unless it is an observational clinical study or in the follow-up phase of an interventional study. 4. Have insufficient washout period for prior anticancer therapy prior to first dose of the study drug. 5. Have major surgery (excluding diagnostic surgery) within 4 weeks prior to the first dose of study drug or anticipation of major surgery during the study. 6. Have prior allogeneic bone marrow transplant or prior solid organ transplant. 7. Have received treatment with systemic steroids. 8. Have received any live vaccine within 4 weeks prior to the first dose of study drug or intend to receive a live vaccine during the study. 9. Leptomeningeal metastases or carcinomatous meningitis, spinal cord compression. 10. Brain metastases with the exceptions. 11. Have uncontrolled or clinically significant cardiovascular and cerebrovascular disease. 12. Have clinically significant concomitant pulmonary diseases. 13. Have a diagnosis of Gilbert's syndrome. 14. Have pleural effusion, abdominal effusion. 15. Have a history of gastrointestinal perforation and or fistula within 6 months prior to the first dose. 16. Have serious infection. 17. Patients with human immunodeficiency virus (HIV) infection. 18. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 19. Have any other primary malignancy within 5 years prior to the first dose of study drug. 20. Have unresolved toxicities from prior anticancer therapy. 21. Have a history of severe hypersensitivity reactions to the drug substance, inactive ingredients in the drug product, or other monoclonal antibodies. 22. Lactating women, or women who are confirmed to be pregnant by pregnancy test within 3 days prior to the first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR assessed according to RECIST v1.1 | By the end of trial date, approximately within 36 months | ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR). |
| Determination of the recommended dose of YL202 in the pivotal clinical study | By the end of trial date, approximately within 36 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) assessed according to RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Clinical benefit rate (CBR) assessed based on RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Depth of response (DpR) assessed based on RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Disease control rate (DCR) assessed based on RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Duration of response (DOR) assessed based on RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Time to response (TTR) assessed based on RECIST v1.1 | By the end of trial date, approximately within 36 months | — |
| Evaluate the overall survival (OS) | By the end of trial date, approximately within 36 months | — |
| Adverse event (AE), described in terms of type, frequency, severity, time, and relationship with study treatment | Approximately within 36 months | — |
| Characterize the PK parameter AUC | Approximately within 36 months | steady-state area under curve (AUC) |
| Characterize the PK parameter Cmax | Approximately within 36 months | peak concentration (Cmax) |
| Characterize the PK parameter Ctrough | Approximately within 36 months | trough concentration (Ctrough) |
| Characterize the PK parameter CL | Approximately within 36 months | clearance (CL) |
| Characterize the PK parameter Vd | Approximately within 36 months | volume of distribution (Vd) |
| Characterize the PK parameter t1/2 | Approximately within 36 months | half-life (t1/2) |
| Incidence of anti-YL202 antibody | Approximately within 36 months | — |
| Evaluate the corelaton between different levels of HER3 expression and the sum of CR rate, PR rate and SD rate | Approximately within 36 months | — |
Countries
China
Contacts
CONTACTMediLink Study Team
Outcome results
None listed